Decision-making modules in protein interaction networks. This project aims to discover how cells use proteins to make decisions. This is important for all living things, which must react to stimuli to grow, adapt, defend themselves and to die. The project’s anticipated outcome is the systems-level identification of decision-making modules in an intracellular network. Its focus is on the smallest possible modules, which contain a decision-making protein with two modifications that control protein ....Decision-making modules in protein interaction networks. This project aims to discover how cells use proteins to make decisions. This is important for all living things, which must react to stimuli to grow, adapt, defend themselves and to die. The project’s anticipated outcome is the systems-level identification of decision-making modules in an intracellular network. Its focus is on the smallest possible modules, which contain a decision-making protein with two modifications that control protein-proteins interactions. It will investigate two recurrent decision-making modules. The expected benefits of the project include new means to decipher biological complexity, and targets to modulate biosystems by genome editing or with drugs.Read moreRead less
The role and regulation of protein methylation: a study using the recently developed methylation network of yeast. Tiny changes to proteins, such as methylation, can alter the way they interact with other proteins. This project will investigate the dynamics of protein methylation during the life of the yeast cell. The project results will be of long term relevance to situations where we may want to stop cells dividing, such as cancer or infectious disease.
Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our ....Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our new multi-layered systems biology strategy to elucidate the first comprehensive understanding of the cell biology that underlies cell state changes. These studies are a major step toward understanding the fundamentals of life. Read moreRead less
The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artifi ....The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artificial regulation of the ribosome may also emerge, relevant to synthetic biology and the engineering of industrial yeasts. The project should provide significant new findings for the research community, generate research citations and contribute to a highly skilled workforce by the training of staff and students.Read moreRead less
Dynamics of atherosclerotic plaque formation, growth and regression. This project aims to provide a mathematical framework to interpret plaque growth. Many biological processes contribute to the growth of atherosclerotic plaques inside arteries. Lipoproteins enter the artery walls and stimulate tissues to signal to cells which duly respond so that fatty streaks form and grow into dangerous plaques that cause heart attacks or stroke. These processes are often nonlinear and operate on widely varyi ....Dynamics of atherosclerotic plaque formation, growth and regression. This project aims to provide a mathematical framework to interpret plaque growth. Many biological processes contribute to the growth of atherosclerotic plaques inside arteries. Lipoproteins enter the artery walls and stimulate tissues to signal to cells which duly respond so that fatty streaks form and grow into dangerous plaques that cause heart attacks or stroke. These processes are often nonlinear and operate on widely varying time scales. The project plans to use systems of ordinary differential equations, partial differential equations with non-standard boundary conditions, and bifurcation theory to find how nonlinear processes shape plaque growth. The expected results may demonstrate the importance of bifurcations, dynamics and nonlinear systems in plaque growth and provide new models to interpret biological data.Read moreRead less
Is FGF21 the master regulator of protein intake? The project plans to bring together two major, rapidly growing disciplines – nutritional geometry and metabolic signalling – to address a topic of fundamental biological significance: the regulation of protein intake. A specific capacity to regulate protein intake has been shown for organisms spanning slime moulds to humans, yet the controlling mechanisms remain elusive. The project aims to test the hypothesis that fibroblast growth factor 21, rel ....Is FGF21 the master regulator of protein intake? The project plans to bring together two major, rapidly growing disciplines – nutritional geometry and metabolic signalling – to address a topic of fundamental biological significance: the regulation of protein intake. A specific capacity to regulate protein intake has been shown for organisms spanning slime moulds to humans, yet the controlling mechanisms remain elusive. The project aims to test the hypothesis that fibroblast growth factor 21, released from the liver under low protein nutrition, is a master regulator of protein intake. Understanding the mechanisms of protein appetite may have implications for organismal biology, understanding social interactions, the structure of food webs and the health and welfare of food and companion animals and humans.Read moreRead less
Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dime ....Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dimension reduction multivariate method developments for data integration. By combining in silico and in vivo approaches, the project is anticipated to benefit scientists willing to work in cutting-edge single-cell research by providing useful protocols and tools to generate novel insights in cell biology. Read moreRead less
Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the pr ....Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the proposed project is to elucidate these important aspects of circRNA biogenesis. Specifically, the project aims to (a) discover proteins that regulate circRNA expression, (b) elucidate how circRNA expression interacts with alternative splicing, and (c) identify circular RNAs that play regulatory roles in gene expression. Read moreRead less
How to build the head: A molecular mechanistic insight. This project aims to gain an insight into the functional output of the gene regulatory network and the molecular determinants that are critical for the formation of the head. Genome-wide sequencing technologies are employed to identify the ensemble of genes that are regulated by Lhx1. By a combination of bioinformatics analysis and a system biology approach, the project aims to build a model of the network of the interacting genes for head ....How to build the head: A molecular mechanistic insight. This project aims to gain an insight into the functional output of the gene regulatory network and the molecular determinants that are critical for the formation of the head. Genome-wide sequencing technologies are employed to identify the ensemble of genes that are regulated by Lhx1. By a combination of bioinformatics analysis and a system biology approach, the project aims to build a model of the network of the interacting genes for head development, and to characterise the function of selected components of this network to refine its architecture and define the dynamics of the network. The knowledge may improve our understanding of the molecular mechanism underpinning the naturally-occurring variation in the forms of major body parts, and of how genes and signals work cooperatively to build an embryo.Read moreRead less
Does phosphorylation regulate the methylation of proteins? . The interaction of proteins is a fundamental requirement of life. Tiny switches on proteins affect how they interact but little is known about how these are controlled. This project will study the complex interplay between two types of switches; one is expected to control the other. This will provide new insights into how the cell functions.